The Hog1 MAP kinase controls respiratory metabolism in the fungal pathogen Candida albicans

Rebeca Alonso-Monge1, Sara Carvaihlo1, Cesar Nombela1

  • 1Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040 Madrid, Spain.

Insights

The Hog1 MAPK pathway in Candida albicans is vital for stress response. Its absence increases fungal sensitivity to respiratory chain inhibitors and alters mitochondrial function, linking MAPK signaling to fungal metabolism.

Area of Science:

  • Molecular Biology
  • Mycology
  • Cellular Respiration

Background:

  • Mitogen-activated protein kinases (MAPKs) are essential for eukaryotic cell signaling.
  • The High Osmolarity Glycerol (HOG) MAPK pathway in Candida albicans regulates stress responses, morphogenesis, and virulence.
  • Understanding MAPK roles is crucial for combating fungal pathogens.

Purpose of the Study:

  • To investigate the role of the Hog1 MAPK in Candida albicans' response to respiratory chain inhibitors.
  • To elucidate the impact of Hog1 deficiency on fungal metabolism and mitochondrial function.
  • To establish a link between MAPK signaling and respiratory metabolism in pathogenic fungi.

Main Methods:

  • Comparative analysis of wild-type and hog1 mutant strains of Candida albicans.
  • Assessment of sensitivity to respiratory chain inhibitors.
  • Measurement of basal respiratory rate and intracellular reactive oxygen species (ROS) levels.
  • Analysis of mitochondrial membrane potential and ATP synthesis.

Main Results:

  • Hog1 deficiency enhances Candida albicans sensitivity to respiratory chain inhibitors.
  • hog1 mutants exhibit increased basal respiration and higher intracellular ROS levels.
  • Mitochondrial membrane potential is altered in hog1 mutants, suggesting increased reliance on mitochondrial ATP synthesis.

Conclusions:

  • The Hog1 MAPK pathway is linked to the regulation of respiratory metabolism in Candida albicans.
  • Hog1-defective mutants display metabolic alterations, including increased dependence on mitochondrial ATP synthesis.
  • These findings provide novel insights into fungal pathogenicity mechanisms and potential therapeutic targets.

Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
C4 Pathway and CAM01:27

C4 Pathway and CAM

Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...